Evidence suggests that serotonin1A (5-HT1A) receptor and benzodiazepine (BZD) receptor function is abnormal in panic disorder (PD), postraumatic stress disorder (PTSD), and depression (MDD). Evidence arguing for a role of BZD/GABA receptor dysfunction in anxiety disorders comes from studies showing anxiolytic and anxiogenic properties of BZD agonists and antagonists, respectively. BZD receptor sensitivity has been shown to be reduced in patients with anxiety disorders. Brain imaging studies using positron emission tomography (PET) and single photon emissison computed tomography (SPECT) suggest decreased BZD receptor binding in PD and PTSD. Yet, association between disturbed interactions between 5-HT1A receptor binding and alterations in BZD receptor binding has not been explored in humans, and so far there are no studies about 5-HT1A receptor binding potential in patients with panic disorder or PTSD. This study will advance knowledge regarding the neurobiology of PD and PTSD by employing PET and [11C]flumazenil and [18F]FC-WAY100635 ([18F]FCWAY) to compare BZD receptor and 5-HT1A receptor binding potential between PD, PTSD, and MDD patients and healthy controls. Because central 5-HT1A receptor density is down-regulated in rodents by corticosterone administration and by stress-mediated corticosterone secretion, assessments of HPA-axis activity will be assessed to determine whether down-regulation of 5-HT1A receptors correlates with cortisol hypersecretion in PD, PTSD, and MDD. During the past year, we have studied 8 subjects with panic disorder, 9 subjects with PTSD, and 4 healthy controls. Because we do not have IRB approval to use C-11 flumazenil to measure benzodiazepine receptors in these patient groups, we have done only the FCWAY portion of the study in these subjects. During the past year, we have continued subject accrual, as detailed in the Narrative Statement to the IRB. The receptor image data have been analyzed, and suggest that a marked reduction in 5HT1A receptor binding exists in panic disorder. This is being reported at international scientific meetings and a manuscript will be submitted this week to report these findings. During the next year we plan to continue subject accrual for FCWAY receptor imaging part of the study, hope to begin the C11 flumazenil portion of the study, and analyze at least the 5HT-1A data of this project.